Effects of α-glucosidase inhibitors on cytochrome P450

我们研究α-glucosidase inhibitors (acarbose and voglivose) on cytochrome P450 （CYP）and hepatotoxicity Of carbon tetrachloride (CCl D24 - D2) and acetaminophen (AP) in rats，both of which ert their toxic effects through bioactivation associated with CYP2E1. We began the与acarbose. Male Sprague-Dawley rots kept on a daily ration (20g) of powdered chowdiet containing 0,20,40 or 80mg / 100g of acarbose，with drinking water containing 0或10% of ethanol (v/v). Three weeks later，the rats were either killed for an vitro metabolism study or challenged with 0.50 g/kg CClD24 po或0.75 g/kg AP ip. The ethanol increased The hepatic microsomal CYP2E1 level and Therate of dimethylnitosamine (DMN) demethylation. The 40 or 80mg / 100g acarbose diet，which alone increased the CYP2E1 level and the rate of DMN demethylationaugmented the enzyme induction by ethanol. the 40或80mg / 100g acarbose diet alone potentiatedCCl - D24 - D2 and AP hepatotoxicityas evidenced by significantly increased levels of both ALT and AST in the plasma of rots pretreatedacarbose. Ethanol alone also potentiated the toxicity of both chemicals. When the 40或80mg/ 100g acarbose diet was combined with ethanolthe ethanol-induced potential/on of CC D24 - D2 and AP hepatotoxicity was augmented. We performedthe similar experiment on voglivose and found it（5.0或10.0 mg/ 100g diet）3 weeks) induced CYP2E1 and increased hepatotoxicity of CC D24 D2 (0.50 g/kg). Our studydemonstrated that high doses of α-glucosidase inhibitors can potentiate CCl D24 - D2 and APhepatotoxicity in rats by inducing hepatic CYP2E1。

We studied the effects of α-glucosidase inhibitors (acarbose and voglivose) on cytochrome P450 (CYP) and hepatotoxicity Of carbon tetrachloride (CClィイD24ィエD2) and acetaminophen (AP) in rats, both of which exert their toxic effects through bioactivation associated with CYP2E1. We began the study with acarbose. Male Sprague-Dawley rots were kept on a daily ration (20 g) of powdered chow diet containing 0, 20, 40 or 80 mg/100 g of acarbose, with drinking water containing 0 or 10% of ethanol (v/v). Three weeks later, the rats were either killed for an in vitro metabolism study or challenged with 0.50 g/kg CCl ィイD24ィエD2 po or 0.75 g/kg AP ip. The ethanol increased the hepatic microsomal CYP2E1 level and the rate of dimethylnitosamine (DMN) demethylation. The 40 or 80 mg/100 g acarbose diet, which alone increased the CYP2E1 level and the rate of DMN demethylation, augmented the enzyme induction by ethanol. The 40 or 80 mg/100 g acarbose diet alone potentiated CClィイD24ィエD2 and AP hepatotoxicity, as evidenced by significantly increased levels of both ALT and AST in the plasma of rots pretreated with acarbose. Ethanol alone also potentiated the toxicity of both chemicals. When the 40 or 80 mg/100 g acarbose diet was combined with ethanol, the ethanol-induced potential/on of CCィイD24ィエD2 and AP hepatotoxicity was augmented. We performed the similar experiment on voglivose and found it (5.0 or 10.0 mg/100 g diet, 3 weeks) induced CYP2E1 and increased hepatotoxicity of CCィイD24ィエD2 (0.50 g/kg). Our study demonstrated that high doses of α-glucosidase inhibitors can potentiate CClィイD24ィエD2 and AP hepatotoxicity in rats by inducing hepatic CYP2E1.